The severe cellular depletion of vitamin B12 (cobalamin, Cbl) in two children congenitally deficient of transcobalamin II (TC II) impaired immunoglobulin production. There was also a defective killing of bacteria by granulocytes in one of these. Both of the lesions of the leukocytes could be reversed and both occurred at phases of Cbl depletion not severe enough to induce morphologic abnormalities of leukocytes or erythrocytes. The present study will explore the mechanisms through which Cbl participates in the production of immunoglobulins and in the antibacterial functions of granulocytes.